In this study, a new application of a keplerate-type giant-ball nanoporous isopolyoxomolybdate, (NH4)42[MoVI72MoV60O372(CH3COO)30(H2O)72], denoted as ({Mo132}), in the synthesis of tetrahydrobenzo[a]xanthene-11-ones via a one-pot, three-component reaction of β-naphthol, aryl aldehydes, and dimedone is reported. The reactions were performed under the solvent-free conditions, providing the corresponding products with high atom economy ranging from 90.77% to 92.32%. The catalyst was prepared using inexpensive and readily available materials and could be easily recovered from the reaction mixture by a simple filtration and reused many times with no significant loss of its catalytic activity. High activity of the catalyst, excellent yields, short reaction time, simple procedure with an easy work-up, and the absence of any volatile and hazardous organic solvents are other advantages of the present methodology.